Chimeric virus-like particles of the human papillomavirus type 16 (HPV 16)as a prophylactic and therapeutic vaccine

Infection by certain human papillomaviruses (HPV), most notably HPV types 1 6 and 18, is the major risk factor for cervical cancer. Worldwide, this dis ease represents the second most frequent malignant tumor in women; thus, th ere is urgent need for efficient therapy and prevention. The natural histor y of cervical cancer and its precursors (cervical intraepithelial neoplasia s), as well as animal experiments, strongly suggest that the immune system controls both the primary infection (by neutralizing antibodies directed ag ainst the major structural protein LI) and the progression of the disease ( via cytotoxic T cells specific for the viral oncoproteins expressed in tran sformed cells, e.g., E7). By the expression of an HPV 16 L1E7 fusion protein, we have generated chime ric virus-like particles (CVLP). Immunization of mice with CVLPs induces ne utralizing antibodies directed against L1 virus-like particles (devoid of t he E7 portion) and E7-specific T cells as measured in vitro. Vaccinated animals are protected against tumor growth following inoculation of syngeneic HPV 16-transformed cells. In addition, we observed a therapeu tic effect of vaccination on pre-existing tumors. This data allowed us to c onclude that CVLPs are suitable for prevention and therapy of HPV infection . A vaccine based on HPV 16 L1E7 CVLPs is currently under development. (C) 1999 IMSS. Published by Elsevier Science Inc.